Human extra-embryonic membranes: role of trophoblast in normal and abnormal pregnancies.

The human embryo is encased in extra-embryonic membranes which are covered with trophoblast throughout pregnancy. Bits and pieces of trophoblast break away from the placenta and are swept into the mother's circulation to lodge in her lungs without causing evidence of inflammation or rejection. This is in part due to an absence of histocompatibility antigens from trophoblast membranes, but it may also be due to a structural glycoprotein which is capable of inhibiting allogeneic recognition and rejection reactions. Another glycoprotein of the trophoblast is shared with lymphocytes, and serological studies have shown this to be polymorphic. Evidence has also been accumulated that this genetically determined cell membrane component is associated with the major histocompatibility complex, and that maternal recognition of this may be necessary to produce blocking factors that protect trophoblast from maternal rejection. Women who lack these factors during pregnancy tend to abort, and some of these patients also share several HLA antigens with their husbands. In an effort to produce blocking factors artificially, four aborting women were immunized with trophoblast-lymphocyte cross-reactive antigens, and this has resulted in normal pregnancies and the delivery of healthy babies at term. This finding suggests that genetical diversity of HLA is associated with TLX antigens, thus providing a mechanism whereby HLA not only generates but is also responsible for the perpetuation of diversity in human populations.